inositol-1-4-5-trisphosphate and Hyperparathyroidism

Lithium-induced hyperparathyroidism is characterized by a reduction in parathyroid sensitivity to changes in extracellular calcium (Ca2+). Ca(2+)-induced transmembrane signal transduction in the parathyroid cell is known to result in the hydrolysis of phosphatidylinositol bisphosphate (PIP2), generating increases in intracellular inositol phosphates, a process which is mediated by a calcium receptor.. To determine if lithium's effect on parathyroid cell function is mediated by an alteration in Ca(2+)-induced hydrolysis of PIP2, inositol 4-monophosphate (IP1), and inositol 1,4,5-trisphosphate (IP3) were measured using anion-exchange chromatography in normal and lithium chloride (LiCl)-treated bovine parathyroid cells at Ca2+ concentrations varying from 0.5 mmol/L to 5.0 mmol/L. IP1 and IP3 concentrations were determined in terms of percent control, defined as the IP1 or IP3 concentration at an [Ca2+] of 0.5 mmol/L.. Increases in [IP1]/10(6) cells (mean +/- standard error of the mean [SEM]) in response to progressive increases in Ca2+ from 0.5 mmol/L to 5.0 mmol/L varied from 825 +/- 228 to 4,474 +/- 382 in control cells versus 1,139 +/- 243 to 4,689 +/- 630 in cells pretreated with LiCl (P > 0.05). The increases in [IP3]/10(6) cells (mean +/- SEM) in response to increases in Ca2+ from 0.5 mmol/L to 5.0 mmol/L, varied from 146 +/- 14 to 385 +/- 35 in control cells versus 134 +/- 16 to 327 +/- 55 in cells pretreated with LiCl (P > 0.05).. Our results demonstrate that LiCl does not effect Ca(2+)-induced hydrolysis of PIP2, suggesting that the desensitizing effect of LiCl on the parathyroid cell is not the result of a Ca2+ receptor-mediated phenomenon.

Topics: Animals; Animals, Newborn; Calcium; Cattle; Cell Membrane; Cells, Cultured; Chromatography, Ion Exchange; Dose-Response Relationship, Drug; Hydrolysis; Hyperparathyroidism; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Lithium Chloride; Parathyroid Glands; Phosphatidylinositol Phosphates; Phosphatidylinositols; Signal Transduction